Effects of developmental exposure to bisphenol A on brain and behavior in mice

Dipartimento di Biologia Evolutiva e Funzionale, University of Parma, Viale Usberti 11A, 43100 Parma, Italy.
Environmental Research (Impact Factor: 4.37). 11/2008; 108(2):150-7. DOI: 10.1016/j.envres.2008.07.023
Source: PubMed


Bisphenol A (BPA) is a widespread estrogenic chemical used in the production of polycarbonate, and epoxy resins lining food and beverage cans and in dental sealants. During fetal life the intrauterine environment is critical for the normal development, and even small changes in the levels of hormones, such as estradiol or estrogen-mimicking chemicals, can lead to changes in brain function and consequently in behavior. We review here a series of ethological studies on the effects of maternal oral exposure during the last part of gestation (prenatal exposure) or from gestation day 11 to postnatal day 7 (perinatal exposure) to a low, environmentally relevant dose of BPA (10 microg/kg bw/day) on behavioral responses of CD-1 mouse offspring. We examined both male and female offspring and found that maternal exposure to BPA affected: (1) behavioral responses to novelty before puberty and, as adults; (2) exploration and activity in a free-exploratory open field; (3) exploration in the elevated plus maze and (4) sensitivity to amphetamine-induced reward in the conditioned place preference test. A consistent effect of the maternal exposure to BPA is that in all these different experimental settings, while a significant sex difference was observed in the control group, exposure to BPA decreased or eliminated the sex difference in behavior. In addition, exposure of female mice to BPA in both adulthood or during fetal life altered subsequent maternal behavior. These findings, together with those from other laboratories, are evidence of long-term consequences of maternal exposure to low-dose BPA at the level of neurobehavioral development.

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    • "BPA is known to have estrogenic properties and to cause adverse health effects in animals. [2] Its effects on mammary glands, [3] on brain and behavioral development, [4] [5] as well as on metabolism and obesity, [6] have been reported. Nevertheless, clear epidemiological evidence of any health effects in humans is still missing. "
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    ABSTRACT: Rationale Due to the growing restrictions on the use of bisphenol A (BPA), several other bisphenols are gaining importance as substitutes for BPA in a variety of applications. There is, therefore, a real need for selective and sensitive methods based on mass spectrometry which will allow the human exposure to these new bisphenols to be assessed. Methods Derivatization of BPA and its substitutes with pyridine-3-sulfonyl chloride is used to enhance the detection capability of bisphenols by electrospray ionization mass spectrometry. A multivariate experimental design, Box-Behnken response surface, was used to evaluate the influence of the main variables potentially affecting the derivatization yield. Fragmentation patterns for all the derivatized bisphenols were acquired by high-resolution/accurate-mass Orbitrap mass spectrometry. Results Temperature and pH were identified as the most important factors affecting the derivatization yield of bisphenols. Fragmentation of the protonated molecules produced abundant analyte-specific product ions. Most of the derivatized bisphenols showed significant improvements in their signal-to-noise ratios compared with the underivatized forms. The stability of these derivatives was demonstrated through several freeze/thaw cycles, short-term room temperature and long-term cold storage. Conclusions Derivatization of BPA and its structural analogues with pyridine-3-sulfonyl chloride is proposed as a specific, sensitive, high-throughput approach to their analysis by liquid chromatography coupled to electrospray ionization mass spectrometry.
    Rapid Communications in Mass Spectrometry 08/2015; 29(16):1473-1484. DOI:10.1002/rcm.7242 · 2.25 Impact Factor
    • "As aquatic compartments, including sediments, often constitute an ultimate reservoir for these compounds, fish could be exposed at various life stages to POPs. Besides such direct exposure, POPs can be transmitted from parents to offspring, through blood during gestation and later in milk, and induce physiological effects in the post-natal period for mammals (Crépeaux et al. 2012, 2013; Palanza et al. 2008; Wormley et al. 2004). For egg-laying species, embryonic exposure occurs mainly through yolk (e.g., for PCBs, see Bodiguel et al. 2009; Daouk et al. 2011; Ottinger et al. 2013). "
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    ABSTRACT: The release of polycyclic aromatic hydrocarbons (PAHs) into the environment has increased very substantially over the last decades. PAHs are hydrophobic molecules which can accumulate in high concentrations in sediments acting then as major secondary sources. Fish contamination can occur through contact or residence nearby sediments or though dietary exposure. In this study, we analyzed certain physiological traits in unexposed fish (F1) issued from parents (F0) exposed through diet to three PAH mixtures at similar and environmentally relevant concentrations but differing in their compositions. For each mixture, no morphological differences were observed between concentrations. An increase in locomotor activity was observed in larvae issued from fish exposed to the highest concentration of a pyrolytic (PY) mixture. On the contrary, a decrease in locomotor activity was observed in larvae issued from heavy oil mixture (HO). In the case of the third mixture, light oil (LO), a reduction of the diurnal activity was observed during the setup of larval activity. Behavioral disruptions persisted in F1-PY juveniles and in their offspring (F2). Endocrine disruption was analyzed using cyp19a1b:GFP transgenic line and revealed disruptions in PY and LO offspring. Since no PAH metabolites were dosed in larvae, these findings suggest possible underlying mechanisms such as altered parental signaling molecule and/or hormone transferred in the gametes, eventually leading to early imprinting. Taken together, these results indicate that physiological disruptions are observed in offspring of fish exposed to PAH mixtures through diet.
    Environmental Science and Pollution Research 02/2015; 22(21). DOI:10.1007/s11356-015-4157-8 · 2.83 Impact Factor
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    • "These alterations paralleled changes in ERRγ (Kundakovic et al., 2013) that may be a basis for altered social behavior. Even in nonsocial behaviors, for example , learning, emotion, and exploration, males and females displayed differential outcomes due to developmental BPA exposures (human: Perera et al., 2012; Braun et al., 2011, 2009; fish: Saili et al., 2012; mice: Jašarevi´c et al., 2013; Kundakovic et al., 2013; Palanza et al., 2008 rats: Jones et al., 2011). These behavioral disruptions are strongly correlated with a range of molecular, physiological, and organlevel mechanisms involved in sex-dependent behaviors, for example, brain ER gene expression (rat: Cao et al., 2013), fetal ovarian and gonadal development (fish: Chung et al., 2011; mice: Kundakovic et al., 2013; Tainaka et al., 2012; Xi et al., 2011a, 2011b; rat: Cao et al., 2013; sheep: Veifa-Lopez et al., 2013), pituitary and gonadotrophin development (mice: Brannick et al., 2012), brain and gonadal enzyme activity (rat: Nanjappa et al., 2012), altered hypothalamic–pituitary–gonadal (HPG) axis activity (mice: Xi et al., 2011a; rats: Ramos et al., 2003), and circulating testosterone levels (mice: Tanaka et al., 2006). "
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    ABSTRACT: Developmental bisphenol A (BPA) exposure is associated with adverse behavioral effects, although underlying modes of action remain unclear. Because BPA is a suspected xenoestrogen, the objective was to identify sex-based changes in adult zebrafish social behavior developmentally exposed to BPA (0.0, 0.1, or 1 μM) or one of two control compounds (0.1 μM 17β-estradiol [E2], and 0.1 μM GSK4716, a synthetic estrogen-related receptor γ ligand). A test chamber was divided lengthwise so each arena held one fish unable to detect the presence of the other fish. A mirror was inserted at one end of each arena; baseline activity levels were determined without mirror. Arenas were divided into three computer-generated zones to represent different distances from mirror image. Circadian rhythm patterns were evaluated at 1-3 (= AM) and 5-8 (= PM) h postprandial. Adult zebrafish were placed into arenas and monitored by digital camera for 5 min. Total distance traveled, percent of time spent at mirror image, and number of attacks on mirror image were quantified. E2, GSK4716, and all BPA treatments dampened male activity and altered male circadian activity patterns; there was no marked effect on female activity. BPA induced nonmonotonic effects (response curve changes direction within range of concentrations examined) on male percent of time at mirror only in AM. All treatments produced increased percent of time at the mirror during PM. Male attacks on the mirror were reduced by BPA exposure only during AM. There were sex-specific effects of developmental BPA on social interactions, and time of day of observation affected results.
    Journal of Toxicology and Environmental Health Part A 01/2015; 78(1):50-66. DOI:10.1080/15287394.2015.958419 · 2.35 Impact Factor
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